Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors |
| |
| Institution: | 1. Biota Scientific Management, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia;2. Biota Europe Ltd, Begbroke Science Park, Begbroke, Oxfordshire OX51PF, United Kingdom;3. Jubliant Chemsys Ltd, B-34, Sector 58, Noida 201301, India;1. Pharmazeutische und Medizinische Chemie, Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany;2. Lehrstuhl für Pharmazeutische Chemie I, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany;3. Lehrstuhl für Pharmazeutische Biologie, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany;1. Ege University, Faculty of Science, Department of Physics, 35100, Bornova, Izmir, Turkey;2. Yozgat Bozok University, Faculty of Art and Sciences, Chemistry Department, 66200, Yozgat, Turkey;3. Ege University, Central Research Testing and Analysis Laboratory Research and Application Center, 35100, Bornova, Izmir, Turkey;4. Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Tandoğan, 06100, Ankara, Turkey;5. Yozgat Bozok University, Faculty of Art & Sciences, Physics Department, 66200 Yozgat, Turkey;1. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China;2. The School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China;1. Laboratoire de Phytochimie et de Pharmacologie, Département de Chimie, Faculté des Sciences Exactes et Informatique, Université Mohamed Seddik Ben Yahia Jijel, B.P. 98 Ouled Aissa, 18000 Jijel, Algeria;2. Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, 1, Avenue de l''Hôpital, B-4000 Liège, Belgium;3. Laboratoire de Physiologie et Pharmacologie, Université Libre de Bruxelles, Faculté de Médecine, 808, Route de Lennik, B-1070 Bruxelles, Belgium;4. Laboratoire “Hypoxie: Physiopathologie Cardiovasculaire et Respiratoire” (HP2), INSERM U1042-Université Grenoble Alpes, F-38042 La Tronche, France |
| |
| Abstract: | A series of dual-targeting, alcohol-containing benzothiazoles has been identified with superior antibacterial activity and drug-like properties. Early lead benzothiazoles containing carboxylic acid moieties showed efficacy in a well-established in vivo model, but inferior drug-like properties demanded modifications of functionality capable of demonstrating superior efficacy. Eliminating the acid group in favor of hydrophilic alcohol moieties at C5, as well as incorporating solubilizing groups at the C7 position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo. |
| |
| Keywords: | DNA gyrase Topoisomerase Antibacterial Synthesis In vivo Dual-targeting |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
